Background: Neuroenhancement (NE), the use of psychoactive substances in order to enhance a healthy individual’s cognitive functioning from a proficient to an even higher level, is prevalent in student populations. According to the strength model of self-control, people fail to self-regulate and fall back on their dominant behavioral response when finite self-control resources are depleted. An experiment was conducted to test the hypothesis that ego-depletion will prevent students who are unfamiliar with NE from trying it. Findings: 130 undergraduates, who denied having tried NE before (43% female, mean age = 22.76 ± 4.15 years old), were randomly assigned to either an ego-depletion or a control condition. The dependent variable was taking an “energy-stick” (a legal nutritional supplement, containing low doses of caffeine, taurine and vitamin B), offered as a potential means of enhancing performance on the bogus concentration task that followed. Logistic regression analysis showed that ego-depleted participants were three times less likely to take the substance, OR = 0.37, p = .01. Conclusion: This experiment found that trying NE for the first time was more likely if an individual’s cognitive capacities were not depleted. This means that mental exhaustion is not predictive for NE in students for whom NE is not the dominant response. Trying NE for the first time is therefore more likely to occur as a thoughtful attempt at self-regulation than as an automatic behavioral response in stressful situations. We therefore recommend targeting interventions at this inter-individual difference. Students without previous reinforcing NE experience should be provided with information about the possible negative health outcomes of NE. Reconfiguring structural aspects in the academic environment (e.g. lessening workloads) might help to deter current users.